Classifications

• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
  • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
  • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
  • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
  • A01N43/12—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings condensed with a carbocyclic ring
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
  • A01N25/12—Powders or granules
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
  • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
  • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
  • A01N25/12—Powders or granules
  • A01N25/14—Powders or granules wettable

Definitions

• the invention concerns substituted 2,3-dihydrobenzofuran compounds and their uses as synergists of insecticide active ingredients.
• synergists Compounds which are no toxic or only slightly toxic against insects, but in combination with active ingredients can produce a new insecticide, having an effectiveness significantly greater than the sum of the components when used separately., are named synergists.
• Metabolism can proceed through oxidative, hydrolytic, conjugative and absorption reactions and possible variations thereof.
• Piperonyl butoxide is claimed to give a synergistic effect in combination with pyrethrins as well as pyrethroids such as allethrin, prallethrin, tetramethrin and so on.
• the inventors of the present invention surprisingly found out that an alkynyl group in the 2,3-dihydrobenzofuran structure confers synergistic activity when combined with the specific linear alkyl chain of 3-6 carbon atoms. Specifically, the selection and the positions of the two substituents in the 2,3-dihydrobenzofuran structure as per Formula (I) gave unexpected synergistic properties as it will be evident from the experimental part.
• the inventors deem that the two specific substituents in positions 5 and 7 of the 2,3-dihydrobenzofuran structure as well as the length of the alkyl chain can interact with the blockade of the enzymes, by a modulation of the binding affinity with the enzymes.
• the invention relates hence to the use of substituted 2,3-dihydrobenzofuran compounds of Formula (I) as synergistic compounds of insecticidal active ingredients.
• the invention relates to an insecticidal composition
• an insecticidal composition comprising at least one insecticidal active ingredient and at least one substituted 2,3-dihydrobenzofuran compound of Formula (I)
• the invention relates to the following specific compounds: 5-n-hexyl-7-((prop-2-ynyloxy)methyl)-2,3-dihydrobenzofuran a compound of formula (I) wherein n is 1, R 1 is H, and R 2 is an n-hexyl substituent; 5-n-hexyl-7-((but-2-ynyloxy)methyl)- 2,3-dihydrobenzofuran) ⁇ a compound of formula(I) wherein n is 1, R 1 is CH 3 , and R 2 is an n-hexyl substituent; 5-n-butyl-7-((but-2-ynyloxy)methyl)-2,3-dihydrobenzofuran a compound of formula (I) wherein n is 1, R 1 is CH 3 , and R 2 is a butyl substituent; 5-n-hexyl-7-(but-2-ynyloxy)-2,3-dihydrobenzofuran,
• the invention relates to the insecticide composition of the invention for use in veterinary medicine.
• the invention relates to the insecticide composition for use in treating pediculosis in humans.
• the present invention concerns a compound of Formula (I)
• n is 1 and, more preferably R 2 is n-butyl or n-hexyl. Still more preferably the compound of Formula (I) is one of: 5-n-hexyl-7-((prop-2-ynyloxy)methyl)-2,3-dihydrobenzofuran), a compound of formula (I) wherein n is 1, R 1 is H, and R 2 is an n-hexyl substituent, having Chemical Formula C 18 H 24 O 2 and Molecular Weight (MW) of 272.38 Dalton whose structure is confirmed by 1 H and 13 C NMR analyses; 5-n-hexyl-7-((but-2-ynyloxy)methyl)-2,3-dihydrobenzofuran, a compound of formula(I) wherein n is 1, R 1 is CH 3 , and R 2 is an n-hexyl substituent having Chemical Formula C 19 H 26 O 2 and Molecular Weight (MW) of 286.41 Dalton whose structure is confirmed by 1 H and 13 C N
• the compound of the invention is more preferably one of:
• the invention concerns an insecticide composition
• an insecticide composition comprising at least one insecticide active ingredient and at least one compound of Formula (I)
• the compounds of the invention can be prepared by a process comprising the following steps:
• the compounds of the invention can be prepared by a process comprising the following steps :
• the insecticide composition of the present invention comprises the present compounds of the formula(I) and an insecticide active ingredient.
• the ratio between the present 2,3-dihydrobenzofuran compound of the formula (I) and the insecticide active ingredient which are contained in the insecticide composition of the present invention is optionally adjustable without limitation according to the control objectives such as kinds of insects, application places, applying times, kinds of the insecticide active ingredient.
• Typical weight ratio of the present compound to insecticide active ingredient is from about 1:100 to about 100:1, preferably from about 1:50 to about 50:1, more preferably from 20:1 to 1:1.
• insecticide active ingredient of the present insecticide composition examples are:
• the insecticide composition of the present invention can also comprise a solid carrier, a liquid carrier and/or a gaseous carrier and, further, if necessary, excipients selected from a surfactant and other adjuvants to have an insecticide formulation.
• the insecticide formulation can contain excipients to have an emulsion, an oil solution, a shampoo preparation, a flowable preparation, a powder, a wettable powder, a granule, a paste, a microcapsule, a foam, an aerosol, a carbon dioxide gas preparation, a tablet, a resin preparation, a paper preparation, a nonwoven fabric preparation, and a knitted or woven fabric preparation.
• excipients to have an emulsion, an oil solution, a shampoo preparation, a flowable preparation, a powder, a wettable powder, a granule, a paste, a microcapsule, a foam, an aerosol, a carbon dioxide gas preparation, a tablet, a resin preparation, a paper preparation, a nonwoven fabric preparation, and a knitted or woven fabric preparation.
• a preparation obtained with the insecticide composition of the present invention contains usually 0.01 to 98% by weight of the present composition with respect to the total weight of the preparation.
• a solid carrier used for the insecticide formulation includes finely-divided powder or granules of clay (e.g., kaolin clay, diatomaceous earth, bentonite, Fubasami clay, acid clay, etc.), synthetic hydrated silicon oxide, talc, ceramics, other inorganic minerals (e.g., sericite, quartz, sulfur, activated carbon, calcium carbonate, hydrated silica, calcium phosphate etc.), hydroxyapatite or chemical fertilizers (e.g., ammonium sulfate, ammonium phosphate, ammonium nitrate, ammonium chloride, urea, etc.); a substance which can be sublimated and is in the solid form at normal temperature (e.g., 2,4,6-triisopropyl-1,3,5-trioxane, naphthalene, p-dichlorobenzene, camphor, adamantan, etc.); wool; silk; cotton; hemp; pulp; synthetic resins (e
• a liquid carrier includes, for example, aromatic or aliphatic hydrocarbons (e.g., xylene, toluene, alkylnaphthalene, phenylxylylethane, kerosene, gas oil, hexane, cyclohexane, etc.), halogenated hydrocarbons (e.g., chlorobenzene, dichloromethane, dichloroethane, trichloroethane, etc.), alcohols (e.g., methanol, ethanol, isopropyl alcohol, butanol, hexanol, benzyl alcohol, ethylene glycol, etc.), ethers (e.g., diethyl ether, ethylene glycol dimethyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, propylene glycol monomethyl ether, tetrahydrofuran, dioxane, etc.), esters (e.g.,
• N-methylpyrrolidone alkylidene carbonates e.g., propylene carbonate, etc.
• vegetable oil e.g., soybean oil, cottonseed oil, etc.
• vegetable essential oils e.g., orange oil, hyssop oil, lemon oil, etc.
• a gaseous carrier includes, for example, butane gas, flon gas, liquefied petroleum gas (LPG), dimethyl ether, and carbon dioxide gas.
• a surfactant includes, for example, alkyl sulfate ester salts, alkyl sulfonates, alkyl aryl sulfonates, alkyl aryl ethers and polyoxyethylenated products thereof, polyethylene glycol ethers, polyvalent alcohol esters and sugar alcohol derivatives.
• adjuvants for formulation include binders, dispersants and stabilizers, specifically, for example, casein, gelatin, polysaccharides (e.g., starch, gum arabic, cellulose derivatives, alginic acid, etc.), lignin derivatives, bentonite, sugars, synthetic water-soluble polymers (e.g., polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid, etc.), PAP (acidic isopropyl phosphate), BHT (2,6-di-t-butyl-4-methylphenol), BHA (a mixture of 2-t-butyl-4-methoxyphenol and 3-t-butyl-4-methoxyphenol), vegetable oils, mineral oils, fatty acids and fatty acid esters.
• binders specifically, for example, casein, gelatin, polysaccharides (e.g., starch, gum arabic, cellulose derivatives, alginic acid, etc.), lignin derivatives, bentonite,
• the insecticide composition contain at least one 2,3-dihydrobenzofuran derivative compound as synergistic compound.
• Other synergists can be present in the composition, also those known in the art such as piperonyl butoxide , MGK 264 and Verbutin
• the present compound can be used in insect control by applying an effective amount of the present compound and a insecticide active ingredient, i.e. the present insecticide composition to insects directly and/or a biotope thereof (e.g., plants, animals, soil, etc.).
• a insecticide active ingredient i.e. the present insecticide composition to insects directly and/or a biotope thereof (e.g., plants, animals, soil, etc.).
• the invention relates to the insecticide composition of the invention for use in veterinary medicine and in yet a further aspect of the invention, the invention relates to the insecticide composition for use in treating pediculosis in humans.
• the application amount is usually 1 to 5,000 g/ha, preferably 10 to 800 g/ha of total amount of the present active ingredient.
• the insecticide composition of the present invention is the form of an emulsion, a wettable powder, a flowable agent, or a microcapsule, it is usually used after dilution with water so as to have the present active ingredient concentration of 0.01 to 1,000 ppm.
• the insecticide composition of the present invention is the form of an oil solution, a powder or a granule, it is usually used as it is.
• preparations as it is may be sprayed as they are to plants to be protected from insects, or may be diluted with water and then sprayed to a plant to be protected from insects.
• Soil can be treated with these preparations to control insects living in the soil. Seedbeds before planting or planting holes or plant feet in planting can be also treated with these preparations.
• a sheet preparation of the insecticide composition of the present invention may be applied by winding around plants, disposing in the vicinity of plants, laying on the soil surface at the plant feet or the like.
• the application amount is usually 0.001 to 100 mg/m 3 of total amount of the present active ingredient for application to space, and 0.001 to 1,000 mg/m 2 of total amount of the present active ingredient for application to a plane.
• the insecticide composition of the present invention is the form of an emulsion, a wettable powder or a flowable agent, it is usually applied after dilution with water so as to have the present active ingredient concentration of 0.001 to 10,000 ppm, preferably 0.01 to 1,000 ppm.
• the insecticide composition of the present invention is the form of an oil solution, an aerosol, a smoking preparation or a poison bait, it is usually applied as it is.
• the insecticide composition in the form of insecticide coil, or an electric insecticide mat is applied by emitting the present active ingredient by heating depending on its form.
• the insecticide composition in the form of a resin preparation, a paper preparation, a tablet, a nonwoven fabric preparation, a knitted or woven fabric preparation or a sheet preparation can be applied, for example, by leaving the preparation as it is in a space to be applied and by sending air to the preparation.
• a space to which the insecticide composition of the present invention is applied for prevention of epidemics includes, for example, a closet, a Japanese-style closet, a Japanese-style chest, a cupboard, a lavatory, a bathroom, a lumber room, a living room, a dining room, a warehouse, and the car inside.
• the insecticide composition may be also applied in outdoor open space.
• the insecticide composition of the present invention When used for controlling parasites living outside of a livestock such as a cow, a horse, a pig, a sheep, a goat or a chicken, or a small animal such as a dog, a cat, a rat or a mouse, it can be used for said animal by a known method in the veterinary filed.
• the insecticide composition is administered, for example, as a tablet, a mixture with feed, a suppository or an injection (e.g., intramuscularly, subcutaneously, intravenously, intraperitoneally, etc.).
• a method of using the insecticide composition of the present invention includes spraying, pour-on treatment or a spot-on treatment with the insecticide composition in the form of an oil solution or an aqueous liquid, washing an animal with the insecticide composition in the form of a shampoo preparation, and attachment of a collar or a ear tag made of the insecticide composition in the form of a resin preparation to an animal.
• total amount of the present active ingredient is usually in the range of 0.01 to 300 mg per 1 kg body weight of the animal.
• Insects against which the insecticide composition of the present invention has controlling effect include harmful arthropods such as insects and mites. More specifically, examples thereof are listed below.
• Delphacidae such as Laodelphax striatellus, Nilaparvata lugens, Sogatella furcifera and the like
• Deltocephalidae such as Nephotettix cincticeps, Nephotettix virescens and the like
• Aphididae such as Aphis gossypii, Myzus persicae and the like, Pentatomidae and Alydidae, such as Nezara antennata, Riptortus clavetus, Eysarcoris lewisi, Eysarcoris parvus, Plautia stali, Halyomorpha mista and the like
• Aleyrodidae such as Trialeurodes vaporariorum, Bemisia argentifolii and the like, Diaspididae, Coccidae and Margarodidae, such as Aonidiella aurantii, Comstocka
• Pieridae such as Pieris rapae and the like
• Tortricidae such as Adoxophyes spp.
• Grapholita molesta Cydia pomonella and the like
• Carposinidae such as Carposina niponensis and the like
• Lyonetiidae such as Lyonetia spp. and the like
• Lymantriidae such as Lymantria spp., Euproctis spp.
• Yponomeutidae such as Plutella xylostella and the like, Gelechiidae such as Pectinophora gossypiella and the like, Arctiidae such as Hyphantria cunea and the like, Tineidae such as Tinea translucens, Tineola bisselliella and the like; Diptera: Culicidae such as Culex pipiens pallens, Culex tritaeniorhynchus, Culex quinquefasciatus and the like, Aedes spp.
• Anopheles spp. such as Anopheles sinensis and the like
• Chironomidae Muscidae such as Musca domestica, Muscina stabulans and the like
• Calliphoridae Sarcophagidae, Fanniidae, Anthomyiidae such as Delia latura, Delia antiqua and the like
• Tephritidae Drosophilidae, Phoridae such as Megaselia spiracularis and the like, sychodidae such as Clogmia albipunctata and the like,
• Scarabaeidae such as Anomala cuprea, Anomala rufocuprea and the like, Rhynchophoridae, Curculionidae and Bruchidae, such as Sitophilus zeamais, Lissorhoptrus oryzophilus, Callosobruchus Kunststoffensis and the like, Tenebrionidae such as Tenebrio molitor, Tribolium castaneum and the like, Chrysomelidae such as Oulema oryzae, Aulacophora femoral is, Phyllotreta striolata, Leptinotarsa decemlineata and the like, Dermestidae such as Dermestes maculates and the like, Anobiidae, Epilachna spp.
• Eriophyidae such as Aculops pelekassi, Aculus Fuendali, and the like
• Tarsonemidae such as Polyphagotarsonemus latus, and the like
• Tenuipalpidae Tuckerellidae
• Ixodidae such as Haemaphysalis longicornis, Haemaphysalis flava, Dermacentor variabilis
• Acaridae such as Tyrophagus putrescentiae, and the like
• Epidermoptidae such as Dermatophagoides farinae, Dermatophagoides ptrenyssnus, and the like
• Cheyletidae such as Cheyletus eruditus, Cheyletus malaccensis
• the insecticide composition of the present invention is preferably suitable for agriculture for professional insect control operators and for household application.
• insecticide composition of the present invention is suitable for the following insect orders: Hemiptera, Diptera, Blattaria, Thysanoptera,Isoptera, and Acarina
• the compound was prepared following the procedure reported in US 6,342,613 starting from 109.3 g(0.5 mol) of hexanoic anhydride (purity 98%), 120.1 g (1.0 mol) of 2,3-dihydrobenzofuran and 6.8 g(0.05 mol) of zinc chloride. The reaction was carried out at 100°C for 4 hrs, cooled down to room temperature, washed with acidic water and the organic phase separated off.
• the organic phase was washed twice with water, dried on anhydrous sodium sulphate, filtered, distilled u.v (55°C / 150 Pa) and subsequently at 133°C/30 Pa, obtaining 107.2 g of a yellow oil product, that was hydrogenated on Pd/C at 140°C/0.6MPa for 7 hrs.
• the organic phase was then added slowly to a mixture prepared by reacting 17.4 g (0.31 mol) of propargyl alcohol and 15.6 g (0.39 mol) of solid sodium hydroxide at 60°C for half an hour. After the addition the mixture is maintained under stirring at 60°C for 4 hrs, cooled down to room temperature and added with 60 ml of NaCl 10% aqueous solution under stirring. The organic solution is then separated off and the solvent evaporated u.v (25°C/50 Pa).
• the organic phase was then added slowly to a mixture prepared by reacting 17.6 g (0.25 mol) of 2-butyn-1-ol and 11.3 g (0.28 mol) of solid sodium hydroxide at 60°C for half an hour. After the addition the mixture is maintained under stirring at 60°C for 10 hrs, cooled down to room temperature and added with 60 ml of NaCl 10% aqueous solution under stirring. The organic solution is then separated off and the solvent evaporated u.v (25°C/500 Pa).
• Substrate used was 7-ethoxycoumarin for inhibition assays as described by Ulrich and Weber (1972) and adapted to microplate format as described by De Sousa et al. (1995). This method had successfully been used previously to characterise inhibition by some piperonyl butoxide analogues against microsomal preparations from whole insects (Moores et al. 2009)
• the compounds of Examples 2-8 therefore show an inhibition activity better than PBO being the percentage of the remaining activity of the enzyme less when the synergists of the invention were used instead of using PBO.
• esterase interference assay was carried out, as being the 'absolute' protocol for characterizing interactions between the compounds of Example 1-9 and FE4.
• this is a protracted method, a selection of products already reported in the literature were used to compare the interference assay and the use of a model substrate.
• Enzyme activity was read at 405 nm in a Spectramax Tmax for 5 min, with readings taken every 5 secs. The rate (mOD min -1 ) was calculated by the integrated software, Softmax Pro v.5.4. A PBO solution (10 mM) was prepared in the same way as a comparison . The results of the percentage of the activity remaining are reported in the Table 2 below.
• the compounds of Examples 1-8 therefore show an inhibition activity better than PBO being the percentage of the remaining activity of the enzyme less when the synergists of the invention were used instead of using PBO.

Landscapes

• Life Sciences & Earth Sciences (AREA)
• Health & Medical Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Organic Chemistry (AREA)
• Chemical & Material Sciences (AREA)
• Wood Science & Technology (AREA)
• Engineering & Computer Science (AREA)
• Dentistry (AREA)
• Plant Pathology (AREA)
• Zoology (AREA)
• Environmental Sciences (AREA)
• Pest Control & Pesticides (AREA)
• Agronomy & Crop Science (AREA)
• Toxicology (AREA)
• Agricultural Chemicals And Associated Chemicals (AREA)

Priority Applications (6)

Applications Claiming Priority (1)

Publications (2)

Family

ID=54072732

Family Applications (1)

Country Status (6)

Families Citing this family (1)

Citations (4)

• 2015
  • 2015-09-09 EP EP15184406.5A patent/EP3141116B1/fr active Active
  • 2015-09-09 ES ES15184406.5T patent/ES2686735T3/es active Active
  • 2015-09-09 PL PL15184406T patent/PL3141116T3/pl unknown
• 2016
  • 2016-09-07 US US15/758,760 patent/US10412961B2/en active Active
  • 2016-09-07 CN CN201680060890.2A patent/CN108471739B/zh active Active
  • 2016-09-07 WO PCT/EP2016/071018 patent/WO2017042185A1/fr not_active Ceased

Patent Citations (5)

Non-Patent Citations (3)

Also Published As

Similar Documents

Legal Events